The invention relates to cancer therapy.
Cancer is a disease manifested by uncontrolled cell growth that presents over 100 distinct clinical pathologies. The development of an effective therapy for such a broad spectrum of disease states represents a unique scientific challenge. Chemotherapeutic agents and radiation, which cause DNA mutations in actively dividing cells, were intended to selectively kill the cancer cells while not effecting normal cells. Unfortunately, these cytotoxic agents, while effective in managing several types of cancer, were limited in their utility due to adverse side effects and lack of specificity for cancer cells. Advancement in our understanding of cell biology and cancer has lead to the advent of new more selective treatments providing hope for cancer patients.
Recent clinical investigations have shown the benefit of combination therapies that target not only the cancer, but its ability to stimulate new blood vessel growth. Angiogenesis, new blood vessel formation, is critical for neoplastic growth and metastasis but is essentially quiescent in adults (I. J. Fidler, L. M. Ellis, Cell, 79, 185 (1994); J. Folkman, Nature Med. 1, 27, (1995)). A number of angiostatic factors such as endostatin (M. S. O'Reilly et. al., Cell 79, 315 (1994)) angiostatin (5. M. S. O'Reilly et. al., Cell 88, 277 (1997)), and thrombospondin have been identified and act to block various steps in the pathway. However, difficulties encountered in production, lack of specificity, and activity levels have combined to detract from the clinical utility of many of these factors.